cgmp aspects of design smp

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SMPSMPSMP ConsultingConsultingConsulting L.L.C.L.L.C.L.L.C.

GMP Aspects of Design

Pharmaceutical Engineering CSUFDesign of Pharmaceutical & Biotech Manufacturing Facilities

8/16/03

Presented bySteve Phillips

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Expected Outcome(s)

• History & Expectations of the GMPs

• Manufacturing Facility Delivery Method….. From Concept to Reality!

• GMP Aspects of Facility Design

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AGENDA

• Introduction 30 sec

• History & Expectations of the GMPs 1 min

• Manufacturing Facility Delivery Method 2 min

• Document Definition/Description 3 min

• Document Definition/Description 3 min

• Motion Picture 30 sec

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History of GMPs

Brief History of Regulations

– 1906—Food and Drug Act Prevent Adulteration

– 1938—Food, Drug & Cosmetic Act Prove Product Safety

– 1962—KeFauver Harris Act Prove Product Efficacy

– 1976—cGMP’s Proposed Clarity(Validation)

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History of GMPs cont.

Typical Product Cycle

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History of GMPs cont.

Compliance Product Life Cycle: GLP/cGMP

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Expectation or Legal Basis for cGMP’s“Adulteration”

A drug is deemed “adulterated” if … The method used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administrated in conformity with current good manufacturing practice (cGMP) to assure that such drug meets the requirements of this chapter as to safety and has identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess………………………….FDC Act § 501 (a) (2) (B)Food, Drug and Cosmetic Act of 1938 FDC Act § 201 (g) (1)

“SSIPpQ”

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Manufacturing Facility Delivery Method

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Infrastructure

General Definition

The basic facilities, services, utilities, and support systems for sustaining production operations and support functions in the most reliable, efficient, and cost effective manner.

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Infrastructure - Delivery

Gown RR

ArchitecturalLayout, Finishes, Flows, etc.

Process

N2 O2 ArCDA

HVAC

Process H2O

Chiller

UtilitiesElectrical

Gas

Water

Scrubber

CVAC

EF

BMS

Parking & Shuttles

Security Cafeteria

Legally Req. & Optional Standby Pwr.

Health & Safety

Distribution

Environmental

Offices

Phone & Data(Accounting/Applications)

UPS

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Development

Test &Commission/Qualify

Production

Scale Up

Idea

Research

Garage

Facilities Planning

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ConstructionCommissioning

andQualification

Startup and Operation

Support

Handover to Client

IQ TestOQ Test

PQIQ ReportOQ Report

Detail DesignSpecification

Conceptual Design

Basic Design

DetailedDesign

Project Proposal

VMP QAP

URS Functional Specification

Impact AssessmentRisk Assessment

IQ ProtocolOQ Protocol

Fat/Sat

DQReview

DQReview

DQApproval

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DQReview

DQReview

DQApproval

ConstructionCommissioning

andQualification

Startup and Operation

Support

Handover to Client

IQ TestOQ Test

PQIQ ReportOQ Report

Detail Design Specification

Conceptual Design

Basic Design

DetailedDesign

Project Proposal

VMP QAP

URS FunctionalSpecification

Impact AssessmentRisk Assessment

IQ ProtocolOQ Protocol

Fat/Sat

User Requirement

Specification (What)

Functional Design (How in Concept)

Detail Design(How to Make)

Implementation

InstallationQualification

Operational Qualification

Performance Qualification

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Document Definition/DescriptionConceptual Design

Basic Design

DetailedDesign

• VMP-Validation Master PlanThe Validation Master Plan (VMP) serves as the validation roadmap, setting the course, justifying the strategy, outlining the preliminary test and acceptance criteria, and documenting the necessary programs that ensure a continuing state of validation.

Typical VMP Contents:1. Introduction2. Scope3. Facility Description4. Commissioning5. Qualification6. Process Validation7. Computer System Validation8. List of Req. Protocols & Procedures9. List of Req. SOP’s10. Equipment & Utility System

Descriptions11. Computer System Description12. Other cGMP Programs13. References

Typical VMP Contents:1. Introduction2. Scope3. Facility Description4. Commissioning5. Qualification6. Process Validation7. Computer System Validation8. List of Req. Protocols & Procedures9. List of Req. SOP’s10. Equipment & Utility System

Descriptions11. Computer System Description12. Other cGMP Programs13. References

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Document Definition/Description

• URS- User Requirement Specifications (customer document)The URS serves as an agreement between production, engineering, validation, and quality assurance for defining what equipment/workspace should do or how to perform. The URS defines the PQ Acceptance Criteria, which tests all functions specified, and shall meet the URS requirements.

Typical URS Contents:1. Laboratory/Workspace Function2. Spatial & Adjacency Requirements3. Room Finishes/Environment4. Basic HVAC Requirements5. VBSE Fume Hoods6. Special HVAC Requirements7. HVAC Process Equipment8. Miscellaneous HVAC Comments9. Plumbing/Process Piping Fixture Requirements10. Equipment Plumbing /Process Piping Requirements11. Electrical Power Requirements12. Electrical Equipment List13. Miscellaneous Electrical Comments14. Lighting15. Signal Systems16. Approval Signatures

Typical URS Contents:1. Laboratory/Workspace Function2. Spatial & Adjacency Requirements3. Room Finishes/Environment4. Basic HVAC Requirements5. VBSE Fume Hoods6. Special HVAC Requirements7. HVAC Process Equipment8. Miscellaneous HVAC Comments9. Plumbing/Process Piping Fixture Requirements10. Equipment Plumbing /Process Piping Requirements11. Electrical Power Requirements12. Electrical Equipment List13. Miscellaneous Electrical Comments14. Lighting15. Signal Systems16. Approval Signatures

“Without first establishingEnd user needs & intended uses, it is virtually impossibleTo confirm that the system can Consistently meet the required Criteria.”

“Without first establishingEnd user needs & intended uses, it is virtually impossibleTo confirm that the system can Consistently meet the required Criteria.”

Conceptual Design

Basic Design

DetailedDesign

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Basic Design

DetailedDesign

• QAP- Quality Activity PlanThe QAP serves as a written plan to establish specific guidelines for preparing and handling the quality documentation. The QAP is established during the Basic Design phase of the project. The quality level of the project is stated in the QAP and defines the activities required to achieve the customer, financial and regulatory requirements. The QAP also includes the Project Execution documents to satisfy Good Engineering Practices (GEP).

Typical QAP Contents:1. General Project Execution Documents/Conditions

(including paperwork & approval sign off flow diagram) 2. Basis of Design3. Vendor/Supplier Criteria and Audit Feedback (inc.

Training).4. Project Budget, Estimates, Letter of Justification5. FAT/SAT Requirements6. Drawings (CAD Standards)7. Submittals, Schedules, Request for Information8. Transmittals, Field Observation Reports, Punch list,

Correspondence, & Change Orders9. Quality Control deviations10. Project Turnover Package & IQD Requirements11. Approval Signatures

Typical QAP Contents:1. General Project Execution Documents/Conditions

(including paperwork & approval sign off flow diagram) 2. Basis of Design3. Vendor/Supplier Criteria and Audit Feedback (inc.

Training).4. Project Budget, Estimates, Letter of Justification5. FAT/SAT Requirements6. Drawings (CAD Standards)7. Submittals, Schedules, Request for Information8. Transmittals, Field Observation Reports, Punch list,

Correspondence, & Change Orders9. Quality Control deviations10. Project Turnover Package & IQD Requirements11. Approval Signatures

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Basic Design

DetailedDesign

• Functional Specification The Functional Specification describes the detailed functions of the equipment (i.e. What the equipment will do), and will be linked to the OQ, which tests all the functions specified.

Typical Functional Specification Example:All low points in the path of the steam shall be equipped with automatic valves and steam traps.The valves shall be in the open position during sterilization and in the closed position during all other phases of the operation.

Typical Functional Specification Example:All low points in the path of the steam shall be equipped with automatic valves and steam traps.The valves shall be in the open position during sterilization and in the closed position during all other phases of the operation.

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Basic Design

DetailedDesign

• Impact Assessment The Impact Assessment is a documented process by which the impact of a system on product quality is evaluated, and the critical components within those systems are identified with a boundary and rationale.

• Risk AssessmentThe Risk Assessment is a documented process by which the design of the facility and its associated appurtenances associated with the project have been evaluated to meet or exceed the requirements of the Food, Drug and Cosmetic Act of 1938. (SSIPpQ) This includes protection of the product, additional products, personnel and buildings.

Impact Assessment Process: Impact Assessment Process: Risk Assessment Example: Risk Assessment Example:

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Basic Design

DetailedDesign

• Detail Design SpecificationsThe Detail Design Specifications is a complete definition of the equipment in sufficient detail to enable it to be built. The DDS are linked to the IQ which checks that the correct equipment is supplied, to the required standards and that it is installed correctly.

• Design QualificationDesign Qualification (Enhanced Design Review) of the 3 phases of design, documented at appropriate stages in a project, for conformance to operational and regulatory expectations.

Typical Detail Design Specifications Examples:1. All piping will slope at 1/16” per lineal ft. to a drain.

2. ½” Sanitary, normally closed, pneumatically actuated, diaphragm valves will be installed in all low points.

3. ½” Sanitary, vertical thermostatic traps shall be installed downstream of the control valves.

Typical Detail Design Specifications Examples:1. All piping will slope at 1/16” per lineal ft. to a drain.

2. ½” Sanitary, normally closed, pneumatically actuated, diaphragm valves will be installed in all low points.

3. ½” Sanitary, vertical thermostatic traps shall be installed downstream of the control valves.

Example DQ (EDR) Team Members:1. Project Manager2. Discipline Engineers3. Design Rep. from Contractors/Vendors4. Operations/Production Representative5. Maintenance Representative6. Quality & Validation Representative7. EHS Representatives

Example DQ (EDR) Team Members:1. Project Manager2. Discipline Engineers3. Design Rep. from Contractors/Vendors4. Operations/Production Representative5. Maintenance Representative6. Quality & Validation Representative7. EHS Representatives

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Basic Design

DetailedDesign

• FAT/SAT- Factory Acceptance Test/Site Acceptance TestThe FAT is test procedures performed either by the customer, the vendor, or 3rd party, at the vendor site to ensure that the equipment meets the customer’s specifications The SAT is a brief re-confirmation of the FAT that took place at the vendors site and has now been shipped to the customers site, or if a FAT was not performed.

• IQ, OQ PQ ProtocolThe IQ, OQ PQ Protocols are detailed system documents describing testing plans, acceptance criteria, and test results that ensure that a system is installed and operates in accordance with predetermined specifications.

Example FAT/SAT Benefits:1. Equipment Test Runs.

2. Identification of design & construction shortcomings.

3. Training and for the Qualification Team

4. Early Data Collection for the IQ,OQ, and PQ .

Example FAT/SAT Benefits:1. Equipment Test Runs.

2. Identification of design & construction shortcomings.

3. Training and for the Qualification Team

4. Early Data Collection for the IQ,OQ, and PQ .

Validation Protocols Example Contents:1. Objective, Scope, & Descriptions2. Responsibilities3. Test Procedures4. Acceptance Criteria5. Deviation Forms (Field Observation Reports)6. Approvals7. Attachments

Validation Protocols Example Contents:1. Objective, Scope, & Descriptions2. Responsibilities3. Test Procedures4. Acceptance Criteria5. Deviation Forms (Field Observation Reports)6. Approvals7. Attachments

NO GMP Aspects Considered in Design & Planning

H.M.S. Titanic


FDA

GMP Aspects Considered in Design & Planning

U.S.S 21CFR

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Acknowledgements

CreatorSteve Phillips

Animation, Sound & Special EffectsHector O. Torres

Steve Phillips

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Acknowledgements

Cast

U.S.S 21CFR………..As GMP Designed

H.M.S. Titanic……………..As Herself

cgmp aspects of design smp

Documents

drug act

drug cosmetic act

history of gmps cont

fdc act

product safety

outcomes history expectations

sec history expectations

cgmpsadulterationa drug